The effects of subclinical levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the response of mice to infection with either Salmonella bern or Herpesvirus suis, also known as pseudorabies virus, are reported. Sublethal levels of TCDD were used: 0.5, 1, 5, 10 or 20 micrograms/kg, given through a gastric tube once weekly for 4 weeks. A significant decrease in weight gain compared with control mice occurred at the 20-micrograms dosage. Dose schedules of 1 micrograms or more, followed by salmonella infection, resulted in significant increases in mortality and decreases in the time from infection to death. However, TCDD had no significant effect on mortality in the pseudorabies-infected mice. The most important finding in this study is that extremely low levels of TCDD, which do not produce clinical or pathological change, still have the capacity to affect host defense.